Molecular Oncology

Molecular Oncology
Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM (IIBM)

Regulation of Androgen Receptor and p53 by HEY1: molecular mechanisms and cancer implications

Transcription factors, such us the Androgen Receptor and the tumour suppressor p53, are key players in the control of the gene expression programs that regulate cell biology. The activity of the transcription factors depends on the recruitment of co-regulators to the promoters of their target genes. Our laboratory has uncovered new roles for the HEY1 co-repressor as a regulator of the Androgen Receptor and p53 transcriptional activity. Furthermore, we have identified through a mass spectrometry-based proteomic approach several proteins that interact with HEY1 that could be important for its function as a transcriptional co-regulator. In addition, a recently performed next-generation sequencing genomic study will help us to identify cell signaling pathways modulated by the expression of HEY1, responsible for the activation of the tumor suppressor p53 and sensitization to anticancer drugs produced by HEY1.

Our global objectives are: to characterize the molecular mechanisms by which HEY1 regulates androgen receptor and p53 transcriptional activity, and to study the possible role of alterations in these molecular mechanisms in the origin and development of tumours. In addition, we will study how these alterations affect the sensitivity of tumor cells to anticancer agents. These objectives, based in the data already obtained through genomic and proteomic approaches, will be pursued combining molecular biology techniques with protein biochemistry and cellular biology by using human cell lines derived from human tumours.

Biomolecules & Cell D.
Molecular Biomedicine